SE460477B

4-substituted imidazo (1,2-alpha) quinoxalines

Abstract

A 1-(2-acylaminophenyl)imidazole of formula: <IMAGE> wherein R2 is hydrogen or a radical bonded to the nitrogen by a carbon to nitrogen linkage and selected from the group consisting of aliphatic, cycloaliphatic, phenyl, substituted phenyl, fused bicyclic aryl, and monocyclic aryl substituted aliphatic groups.

SE460477B, drawing sheet 1 — Sheet 1 of 70

Term

No projected expiry on record.

4 claims: 1 independent, 3 dependent

1
PATENTKRAV 1. Mellanprodukter, kännetecknade därav, att de är l-(2-acylaminofenyl)imidazoler med formeln vari X är -R* eller -NHR 2 , där R^· är <1) rak. eller grenad alkyl med 1-18 kolatomer, (2) alkenyl med 1-18 kolatomer, <3) alkoxialkyl med 1-4 kolatomer i alkyldelen, (4) halogenalkyl, (5) cykloalkyl med 3-8 kolatomer, (6) cykloalkenyl med 5-6 kolatomer, (7) mono-, di- eller trisubstituerad fenyl, varvid aubatituenten eller substituenterna utgörs av rak eller grenad alkyl med 1-6 kolatomer, alkoxi med 1-6 kolatomer, hydroxi, acyloxi med 1-18 kolatomer, halogen, nitro, amino, acylamino, där acylgruppen härrör från en alkansyra med 1-18 kolatomer;bensamido, vari bensenringen är osubstituerad, eller monosubstituerad, disubstituerad eller trisubstituerad med alkylgrupper innehållande 1-5 kolatomer eller med halogenatomer;cyano, trifluormetyl, alkyltio, karboxyl, fenyl eller fenoxi, som eventuellt är substituerad med hydroxi eller metoxi, <8) bensyl, (9) fenoximetyl, (10) styryl eller (11) naftyl och R 2 är Cl) lägre alkyl, (2) cykloalkyl med 3-8 kolatomer, (3) fenyl eller mono- eller disubstituerad fenyl, varvid substituenten eller substituenterna utgörs av rak eller grenad alkyl med 1-6 kolatomer, halogen, 460 477 nitro, cyano, trifluormetyl, alkyltio eller fenoxi, eller (4) naftyl, vilka mellanprodukter är avsedda för framställning av 4-subsituerade imidazoC1,2-a)kinoxaliner med formeln och farmaceutiskt godtagbara salter därav, vari X har ovan angiven betydelse.
2
Mellanprodukter enligt krav 1, kännetecknade därav, att X är -R*.
3
Mellanprodukter enligt krav 1, kännetecknade därav, att X är -NHR 2 .
4
Mellanprodukter enligt krav 3, kännetecknade därav, att R 2 är lägre alkyl.

Independent claims4

993 paragraphs in 45 sections, as filed

(54) NAME 1- (2-acylaminophenyl) imidazoles for use as intermediates (56) PUBLICATIONS REFERRED TO: ---

OTHER PUBLICATIONS: Chemical Abstracts 9 Coll. Vol. 76-85, 1972-1976, Ethaneseleneno-F, p. 16512cs, Formamide, N- / 2 ~ (1H-imidazoll-yl) phenyl7 (57) SUMMARY:

The invention relates to novel intermediates for the preparation of 4-substituted imidazo (1,2-a) quinoxalines, which intermediates are characterized as being 1- (2-acylaminophenyl) imidazoles of the formula

ON 1M ί 182 AA. . 12 Wherein X is -R or -NHR, wherein R * is a further defined aliphatic or cycloaliphatic group as defined in claim 1, a substituted phenyl or condensed bicyclic aryl group or a monocyclic aryl substituted aliphatic bond attached to the carbonyl carbon atom via a carbon-carbon bond, and R 2 is a group which is bonded to the nitrogen via a carbon-nitrogen bond and is constituted by an aliphatic or cycloaliphatic group as defined in claim 1, a phenyl, substituted phenyl or condensed bicyclic aryl group.

Sitfroma mom brackets anoer mtemationeB kSentiterinastod. tNiD code Letter «after pinching ano« ntemaboneS dofajmerttod.

,460 477

The present invention relates to certain 1- (2-acylaminophenyl) imidazoles which are useful as intermediates in the preparation of 4-substituted imidazo / 1,2-a / quinoxalines, which compounds are useful for a variety of purposes. Some of said compounds are useful as immunosuppressive agents while others have use as anti-inflammatory agents or exhibit antifungal action. Furthermore, some compounds exhibit two of these effects or all three effects.

The 4-substituted imidazo / 1,2-α / quinoxalines can be illustrated by the formula

460 477 or pharmaceutically acceptable salts thereof, wherein X represents -R 21 or -NHR, wherein R is bonded to a ring carbon atom by a carbon-carbon bond and is an aliphatic or cycloaliphatic group, a substituted phenyl or condensed bicyclic aryl group or a monocyclic, aryl-substituted aliphatic group and R is a group bonded to a nitrogen atom by a carbon-nitrogen bond and is an aliphatic or cycloaliphatic group or a phenyl, substituted phenyl or condensed bicyclic aryl group.

The novel melanic products of the invention useful in the preparation of the compounds of formula I have the formula

II

2 "Wherein X is -R or -NHR, where R * is (1) straight or branched alkyl of 1-18 carbon atoms, (2) alkenyl of 1-18 carbon atoms, (3) alkoxyalkyl of 1-4 carbon atoms in the alkyl moiety, ( 4) haloalkyl, (5) cycloalkyl with

3-8 carbon atoms, (6) cycloalkenyl of 5-6 carbon atoms, (7) mono- or di-trisubstituted phenyl, the substituent or substituents being straight or branched alkyl of 1-6 carbon atoms, alkoxy of 1-6 carbon atoms, hydroxy, acyloxy of 1-18 carbon atoms, halogen, nitro, amino, acylamino, wherein the acyl group is derived from an alkanoic acid having 1-18 carbon atoms; benzamido, wherein the benzene ring is unsubstituted or monosubstituted, disubstituted or trisubstituted with alkyl groups containing 1-5 carbon atoms or with halogen atoms; cyano, trifluoromethyl, alkylthio, carboxyl, phenyl or phenoxy optionally substituted by hydroxy or methoxy, (8) benzyl, (9) phenoxymethyl, (10) styryl or (11) naphthyl and R2 are (1) lower alkyl, (2) cycloalkyl of 3-8 carbon atoms, (3) phenyl or mono- or disubstituted phenyl, the substituent or substituents being straight or

460 477 branched alkyl of 1-6 carbon atoms, halogen, nitro, cyano, trifluoromethyl, alkylthio or phenoxy, or (4) naphthyl.

Examples of aliphatic groups covered by R are as follows:

CH3~; CH3CH2-; CH3CH2-CH2-; CH3(CH2)nwherein when 3, 4, 5, 6, 7, 8, 14 and 16, respectively; (CH3)2CH-CH2-; CH3(CH2) (CH3CH2) CH-;

CH2= CH- (CH2) Θ-; methoxymethyl; CH2-C1-; CH3CHC1-; CHC12-; CC13~; CH2Br; CF3·

As examples of cycloaliphatic groups included in R1,); cyclobutyl (ie);

may be mentioned cyclopropyl (i.e.

cyclohexyl; and cyclohexenyl (ie). i.

ί * Λ 'z

In general, the compounds of formula I above can be prepared by heating the corresponding 1- (2-acylaminophenyl) imidazole of formula II under reflux in the presence of cyclizing amounts of a cyclizing agent, e.g. polyphosphoric acid or phosphorus oxychloride, for a time sufficient to effect substantial cyclization of this reactant.

The above reaction can be illustrated by the following reaction formula:

III

The process of reaction formula III is preferably carried out in the presence of an excess of an organic solvent in the form of an amine. A variety of solvents may be used for this purpose and the following solvents may be particularly mentioned: pyridine, 2,6-dimethylpyridine, Ν, Ν-dimethylaniline, trimethylamine and N-methylmorpholine. The preferred organic solvent is pyridine.

u460 477

The amount of phosphorus oxychloride used in the reaction may vary slightly. In general, however, the phosphorus oxychloride is used in an amount of from about 1/2 mole to about 6 moles and preferably from 1/2 mole to 2 moles per mole of compound II.

The desired product I can be recovered from the reaction mixture using conventional techniques as will be apparent to those skilled in the art. The reaction time may vary depending, among other things. on the particular reactants or molar amounts of the reactants used. Generally, the reaction time is from about 30 to 120 minutes.

The temperature employed in conducting the reaction also varies depending on the particular reactants selected, the solvent and other factors. Usually, the temperature used is the reflux temperature of the reaction mixture. This is usually in the range of about 95 ° C to 195 ° C.

The manner of preparing the 1- (2-acylaminophenyl) imidazoles of formula II varies depending on the particular type of matter to be prepared. In the preparation of compounds of dsn general formula

460 477 of an excess of the solvent (e.g. pyridine) under reflux. When the compounds in question are of the phenylureylene type, i.

wherein R is as defined above, these are prepared by reacting the aminophenylimidazole with the appropriate isocyanate. This reaction can be illustrated by the following reaction formula:

The reaction is preferably carried out in the presence of a solvent and at steam bath temperatures. A typical solvent that can be used is toluene, and the reactants are usually used in approximately equimolar amounts. The products obtained by the above reactions can be recovered using standard techniques well known to those skilled in the art.

Preparation of 1- (2-acylaminophenyl) imidazoles

The 1- (2-acylaminophenyl) imidazoles of the present invention are prepared in accordance with the general procedures described above. Tables Σ-IV below indicate the particular process in question which has been used to prepare each compound and also shows the physicochemical properties of the compound obtained. The melting points were obtained using the capillary tube method using a Mel-Temp melting point apparatus and are uncorrected. Ultraviolet spectra were obtained in ethanol solution using the instrument ·, Beckman UV Acta III or Beckman DBG. 1- (2-Aminophenyl) imidazole was prepared according to the method of AF Pozharskii,

460 477

AM Siminov and LM Sitkina in Khim. Geterotskl. Soedin. 5 (1969) 1916 / Chem. Abstr. 72, (1970) 11427A/.

Table I below illustrates the preparation of the aliphatic, cycloaliphatic, and monocyclic aryl-substituted aliphatic amidophenylimidazoles of the present invention. Table II illustrates the preparation of the aryl (including the ring-fused aryl) amidophenylimidazoles of the present invention.

With the exceptions set forth in Tables I and II, the amides were prepared by reacting equimolar amounts of the appropriate acid chloride in question with 1- (2-aminophenyl) imidazole in the presence of an excess pyridine on a steam bath for 45 minutes. The reaction mixture was then stirred in ice water and the crude product was isolated by any of the following methods. '

Method A. If your solid was obtained, it was crystallized directly from the solvent given in Table I.

Method B. If an oil was obtained, it was dissolved in the least amount of chloroform and passed through an alumina column, the amount of alumina being about 20 times the weight of the solid crude product; elution was carried out with chloroform. The chloroform was stripped of the crude product which crystallized as given in Table I.

Method C. If a solution was obtained in ice-water mixture, the pyridine / water azeotrope was removed until the crude product precipitated. This was then treated as indicated under the Bovan method.

460 477

Table I

1- (2-alkanamidofenyl) imidazoles

<td rowspan="2">Nr.</td><td rowspan="2">R</td><td rowspan="2">isolation Method</td><td rowspan="2">Exchange %</td><td rowspan="2">crystallisation rsolution - average ° C</td><td colspan="3">Analysis</td>

<td colspan="2">calculated</td><td>Found</td>

<td> 2</td><td>CH -</td><td>A</td><td> 56,2</td><td>Ethanol 163-166</td><td>C</td><td> 65,66</td><td> 65,69</td>

<td> 3</td><td rowspan="2">CH3CH2-b</td><td>C</td><td> 73,9</td><td>Water 144-146</td><td>C</td><td> 66,96</td><td> 67,26</td>

<td> 4</td><td rowspan="2">CH3(CH2)2-</td><td>B</td><td> 31,1</td><td>Toluene 108-110</td><td>C</td><td> 68,10</td><td> 67,95</td>

<td> 5</td><td>CH3(CH2)3-</td><td>B</td><td> 49,6</td><td>Toluene- 123-125</td><td>C</td><td> 69,11</td><td> 69,14</td>

<td></td><td>0 C 0</td><td></td><td></td><td>hexane</td><td>Η</td><td> 7,04</td><td> 7,00</td>

<td> 6</td><td rowspan="2">CH3(CH2)4-</td><td>B</td><td> 49,4</td><td>Isopropyl 103-105</td><td>C</td><td> 70,01</td><td> 70,31</td>

<td></td><td></td><td></td><td>ether-tri-</td><td>Η</td><td> 7,44</td><td> 7,45</td>

<td></td><td></td><td></td><td></td><td>chloroethylene</td><td>Ν</td><td> 16,33</td><td> 16,26</td>

<td> 7</td><td>CH3(CH2)5-</td><td>A</td><td> 55,3</td><td>isopropyl- 96-98</td><td>C</td><td> 70,82</td><td> 70,79</td>

<td></td><td></td><td></td><td></td><td>ether</td><td>Η</td><td> 7,80</td><td> 7,74</td>

<td> 8</td><td rowspan="2">CH3(CH2)6-</td><td>A</td><td> 55,1</td><td>Isopropyl 101-102</td><td>C</td><td> 71,55</td><td> 71,67</td>

<td></td><td></td><td></td><td>ether</td><td>Η</td><td> 8,12</td><td> 8,05</td>

<td> 9</td><td rowspan="2">CH3(CH2)7-</td><td>A</td><td> 45,6</td><td>Isopropyl 93-95</td><td>C</td><td> 72,21</td><td> 72,24</td>

<td></td><td></td><td></td><td>ether</td><td>Η</td><td> 8,42</td><td> 8,41</td>

<td> 10</td><td rowspan="2">CH3(CH2)8-</td><td>A</td><td> 60,6</td><td>Isopropyl- 79-81</td><td>C</td><td> 72,81</td><td> 73,38</td>

<td></td><td></td><td></td><td>ether-hexane</td><td>Η</td><td> 8,68</td><td> 8,85</td>

'OMBSäS

460

A «7 * 7 * t / i

<td rowspan="2">Nr.</td><td rowspan="2">R</td><td rowspan="2">isolation Method</td><td rowspan="2">Yield%</td><td rowspan="2">Crystal licensing solvent</td><td>Mp.</td><td></td><td>Analysis</td><td></td>

<td>0 ° C</td><td colspan="2">3era'knat</td><td>Found</td>

<td> 11</td><td>Chrs3 (Chrs2)14-</td><td>B</td><td> 58,1</td><td>ether</td><td> 94- 96</td><td>CH</td><td> 75,52 9,89</td><td> 75,12 9,76</td>

<td> 12</td><td>CH3(CH2)16-</td><td>B</td><td> • 80,6</td><td>isopropyl</td><td> 98-100</td><td>C</td><td> 76,19</td><td> 76,57</td>

<td></td><td></td><td></td><td></td><td>ether</td><td></td><td>hrs</td><td> 10,18</td><td> 10,28</td>

<td> 13</td><td>(CH3)3Cb</td><td>C</td><td> 48,8</td><td>Benzene</td><td> 102-104</td><td>C</td><td> 69,11</td><td> 69,15</td>

<td> 14</td><td>(CH9)9CHCH9-</td><td>C</td><td> 25,4</td><td>Benzene</td><td> 128-130</td><td>C</td><td> 69,40</td><td> 69,60</td>

<td> 15</td><td colspan="2">Chrs3(CH2)3(CH3CH2)CH- B</td><td> 32,8</td><td>Benzene</td><td> 125-127</td><td>CH</td><td> 71,55 8,12</td><td> 71,86 7,84</td>

<td> 16</td><td>CH9«CH- (CH9)„-</td><td>A</td><td> 76,8</td><td>isopropyl</td><td> 92- 94</td><td>C</td><td> 73,81</td><td> 74,26</td>

<td></td><td>£ £ o</td><td></td><td></td><td>ether-hexane</td><td></td><td>hrs</td><td> 8,36</td><td> 8,50</td>

<td> 18</td><td rowspan="2"> 0^4-</td><td>C</td><td> 41,9</td><td>Ethanol</td><td> 145-147</td><td>CH</td><td> 73,63 5,45</td><td> 73,81 5,57</td>

<td> 20</td><td>^^ - gr cii-</td><td>A</td><td> 43,0</td><td>Ethanol</td><td> 161-164</td><td>CH</td><td> 74.72 5,23</td><td> 74,94 5,47</td>

<td> 21</td><td>CH9and9-</td><td>A</td><td> 49,8</td><td>TolueB</td><td> 146-147</td><td>C</td><td> 62,33</td><td> 61,99</td>

<td> 22</td><td>ο-θ-α.2</td><td>. A</td><td> 77,7</td><td>Tolueri</td><td> 136,5- 138,5</td><td>C hrs</td><td> 69,61 5,15</td><td> 69,82 5,37</td>

<td> 23</td><td> >·- :</td><td>A</td><td> 10,1</td><td>isopropanol</td><td> 207-209</td><td>CH</td><td> 68,71 5,76</td><td> 68,67 5,85</td>

W '

460 477

<td>Nr.</td><td>R</td><td>isolation Method</td><td>Yield%</td>

<td rowspan="2">Crystallization Solvent</td><td rowspan="2">Mp. ° CE</td><td colspan="2">Analysis</td>

<td>Jeräknat</td><td>Found</td>

<td>toluene</td><td> 151-153</td><td>C, 69.69</td><td> 69,44</td>

<td>toluene</td><td> 142,5-</td><td>C, 71.35</td><td> 70,88</td>

<td>Ethanol</td><td> 196-</td><td>C, 72.16</td><td> 71,87</td>

<td>Water</td><td> 255</td><td>C, 56.06</td><td> 55,92</td>

<td>toluene</td><td> 143,5-</td><td>C, 57.72</td><td> 57,54</td>

<td>Benzene</td><td> 162-165</td><td>C, 48.91</td><td> 48,94</td>

<td>Ethanol</td><td> 165-167</td><td>C, 51.77</td><td> 51,58</td>

<td>Remarks:</td><td>b. Prepared via the anhydride. c. Could not crystallize; was purified by chromatography on alumina with ethyl acetate as eluent.</td>

460 477

Table II

NHC-Ar

<td colspan="4">L- (2-arylamidofenyl) imidazoles</td>

<td>Nr.</td><td>Are</td><td>Insole Trout byte method%</td><td>Crystallization <Solution Xmp· Average ° C</td>

Amax. (AM)

<td> 35</td><td></td><td>A</td><td> 58,7</td><td>ethanol</td>

<td> 36</td><td>P CH</td><td>B</td><td> 58,3</td><td>benzene</td>

Analysis__

Don't worry

<td>57.4 benzene</td><td> 143-</td><td colspan="2">236 (23,400) C 73.63</td><td> 73,28</td>

CU3,JCJO*

A 53.0 benzene

151-153

C, 61.6360.97

H, 3,653.62

N, 12.6812.34

79.3 ethyl acetate 136-138

45.5 isopro- 198-200 panol

73.5 dimethyl 194-196 formamide, ethanol

460 477

Crystal i-

<td rowspan="2">Are</td><td rowspan="2">isolation Method</td><td rowspan="2">Yield%</td><td rowspan="2">cation solution *p· Average ° C</td><td rowspan="2">Amax. (AM)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td rowspan="2">Q-</td><td>A</td><td> 74,4</td><td>dimethyl-198-</td><td rowspan="2"> 250(16 500)</td><td>C, 62.13</td><td> 62,27</td>

<td></td><td></td><td>formamide/202.5 water</td><td>H, 3.92 N, 18.17</td><td> 4,00 18,37</td>

<td>UO2 NO2 / = \</td><td>A</td><td> 87,41</td><td>dimethyl 254-256</td><td>c.</td><td>C, 54.40</td><td> 54,35</td>

<td></td><td></td><td></td><td>formamide,</td><td></td><td>H, 3.14</td><td> 3,31</td>

<td>f no2</td><td></td><td></td><td>water</td><td></td><td>N, 19.82</td><td> 19,82</td>

<td>ust-0-</td><td>A</td><td> 60,87</td><td>dimethyl 219-</td><td> 234(1 500)</td><td>C, 70.82</td><td> 70,14</td>

<td></td><td></td><td></td><td>formamide, 220.5</td><td></td><td>H, 4.20</td><td> 4,45</td>

<td></td><td></td><td></td><td>water</td><td></td><td>N, 19.49</td><td> 19,15</td>

<td>O-.</td><td>B</td><td> 56,8</td><td>benzene 205-208</td><td> 229(18 500)</td><td>C, 68.32 H, 4.30</td><td> 67,86 4,02</td>

<td>Q</td><td>A</td><td> 53,2A</td><td>dimethyl</td><td></td><td></td><td></td>

<td>F</td><td></td><td></td><td colspan="2">formamide. 93-96 260 (10 100)</td><td>C, 66.20</td><td> 65,96</td>

<td></td><td></td><td></td><td>water</td><td></td><td>H, 4.51</td><td> 4,37</td>

<td rowspan="3">O*</td><td>A</td><td>b.</td><td>dimethyl 189-</td><td> 240(22 100)</td><td>C, 56.16</td><td> 56,03</td>

<td></td><td></td><td>formamide 190.5</td><td></td><td>H, 3.53</td><td> 3,58</td>

<td rowspan="2">Q '</td><td>A</td><td> 40,1</td><td>di methyl 199</td><td> 258(20 100)</td><td>C, 56.16</td><td> 55,84</td>

<td></td><td></td><td>formamide, 201.5</td><td></td><td>H, 3.54</td><td> 3,58</td>

<td>No</td><td></td><td></td><td>water</td><td></td><td>N, 12.28</td><td> 12,48</td>

<td rowspan="2">Q</td><td>A</td><td> 38,7</td><td colspan="2">dimethyl 201-203 261 (16,700)</td><td>C, 64.54</td><td> 64,70</td>

<td></td><td></td><td>formamide,</td><td></td><td>H, 4.06</td><td> 4,05</td>

<td>Cl</td><td></td><td></td><td>ethanol</td><td></td><td>N, 14.11</td><td> 13,95</td>

<td>Q '</td><td>. B</td><td> 68,5</td><td>ethanol 144-146</td><td>c.</td><td>C, 64.54 H, 4.06</td><td> 64,82 3,92</td>

<td>O-</td><td>A</td><td> 59,7</td><td>ethanol 167-170</td><td> 240(26 410)</td><td>C, 64.54 H, 4.06</td><td> 64,41 3,94</td>

<td>-Q</td><td>A</td><td> 26,6</td><td>dimethyl 210-212</td><td rowspan="2"> 265(21 000)</td><td>C, 57.85</td><td> 58,05</td>

<td>Cl</td><td></td><td></td><td>formamide,</td><td>H, 3.34</td><td> 3,46</td>

<td></td><td></td><td></td><td>water</td><td></td><td>N, 12.65</td><td> 13,08</td>

1460 477 v

Nr. Are

Crystal Insulation s ring exchange solution "P* method% average ° C Λ max, (Am)

Analysis

Do not find

<td>A</td><td> 61,2</td><td>dimethylformamide water</td><td> 180,5- 235(22 100) , 183</td><td colspan="2">C, 57.85 H, 3.34 N, 12.65</td><td> 57,65 3,51 12,93</td>

<td>A</td><td> 42,9</td><td>ethanol</td><td> '186,5- 255(28 480)</td><td>C</td><td> 49,38</td><td> 49,22</td>

<td>58.6 isopro 146-151 263 (20,400)</td><td>C</td><td> 69,61</td><td> 69,01</td>

<td>propanol</td><td>hrs</td><td> 5,15</td><td> 5,14</td>

<td>p ·</td><td>B</td><td>83.2 Dimethyl 171-173281 (5100)</td><td colspan="2">C, 69.61</td><td> 69,27</td>

<td rowspan="2">And J</td><td></td><td>formamide,</td><td>hrs</td><td> 5,15</td><td> 5,02</td>

<td></td><td>water</td><td>N</td><td> 14,33</td><td> 14,28</td>

<td>p</td><td>B</td><td>61.2 benzene 130-224sh</td><td>C</td><td> 66,86</td><td> 66,97</td>

<td> < />'</td><td>c</td><td> 29,79</td><td>dimethyl 133.5-281 (15,410)</td><td>C</td><td> 69,61</td><td> 69,10</td>

<td></td><td></td><td></td><td>formamide, 136.5</td><td>hrs</td><td> 5,15</td><td> 5,08</td>

<td>AND3</td><td></td><td></td><td>water</td><td>N</td><td> 14,33</td><td> 14,18</td>

<td>p ·</td><td>B</td><td> 18,26</td><td>dimethyl 164.5-c.</td><td>C</td><td> 56,16</td><td> 55,65</td>

<td>No</td><td></td><td></td><td>formamide, 166.5</td><td>hrs</td><td> 3,54</td><td> 3,51</td>

<td></td><td></td><td></td><td>water</td><td>N</td><td> 12,28</td><td> 12,37</td>

<td>A</td><td>51.07 isopro-</td><td> 142,5-223(14 420)</td><td>C, 68.32</td><td> 67,79</td>

<td></td><td>propanol</td><td> 145,5</td><td>H, 4.30</td><td> 4,36</td>

FF

FF

<td rowspan="2">B</td><td rowspan="2"> 15,68</td><td rowspan="2">isopropanol ethanol</td><td rowspan="2"> 203,5-258(18 840) 205</td><td colspan="2">C, 54.40</td><td rowspan="2"> 53,78 2,30 12,16</td>

<td>A</td><td> 46,9</td><td>isopropyl</td><td> 165,5- 237(53 900)</td><td>C</td><td> 76,66</td><td> 76,29'</td>

<td></td><td></td><td>propanol</td><td>167J5</td><td>hrs</td><td> 4,83</td><td> 4,84</td>

IN

460 477 ί

Heat

benzene ethanol in sopropanol dimethylformamide

Crystallization Solvent

Mp. ° C

Tlmax. (AM)

175-177

156157,5

134136,5

289(6 940)

268(13 800)

273 (14 900)

calculated

C

H ri

Found

76,66

4,82

13,41

76,68

4,75

12,01

64,58

5,42

11,89

64,58

5,39

12,09

66,86

5,30

13,00

66,88

5,37

12.68 such as hemihydrate. loss prevented exchange determination.

Notes: a. Isolated

b. partial

c. the compound showed too low absorption to allow significant UV determination.

The alkyl 2- (1-imidazolylphenylureylenes (Table III)) were prepared by reacting equimolar amounts of the aminophenylimidazole and the appropriate isocyanate in toluene solution at steam bath temperature for 2 or 3 hours. :

(A) Direct crystallization from the appropriate solvent in question or (B) Dissolution in hot dimethylformamide and precipitation with water followed by crystallization.

460 477

Alkyl 2- (1-imidazolyl) phenylureylenes

crystal-

<td rowspan="3">Nr.</td><td rowspan="3">R</td><td colspan="2" rowspan="2">Insole Exchanging bytes</td><td rowspan="3">sationslösningsmedel</td><td rowspan="3">Mp. ° C</td><td rowspan="3">ANW. (Ara)</td><td colspan="2">Analysis</td>

<td rowspan="2">calculated</td><td rowspan="2">Found</td>

<td>method</td><td> 2</td>

<td> 64</td><td>CH_-</td><td>A</td><td> 41,6</td><td>ethanol</td><td> 194-</td><td> 240(15 500)</td><td>C, 61.60</td><td> 61,22</td>

<td> 65</td><td>CH, CH0-</td><td>B</td><td> 27,3</td><td>trichloro-</td><td> 173-</td><td> 278(1 200)</td><td>C, 62.59</td><td> 62,21</td>

<td></td><td>Ο ά</td><td></td><td></td><td>ethyl one</td><td> 175</td><td> 242(12 700)</td><td>H, 6.13</td><td> 6,04</td>

<td> 66</td><td>CH, CH9CH -</td><td>B</td><td> 49,3</td><td>trichloro-</td><td> 139-</td><td> 279(1 200)</td><td>C, 63.92</td><td> 63,75</td>

<td></td><td>0 ά c</td><td></td><td></td><td>ethyl one</td><td> 141</td><td> 240(12 800)</td><td>H, 6.60</td><td> 6,56</td>

<td> 67</td><td>CH, CH0CH "CH0-</td><td>B</td><td> 35,6</td><td>i sopro-</td><td> 115-</td><td> 278(1 400)</td><td>C, 65.09</td><td> 64,84</td>

<td></td><td>43 & t · XZ</td><td></td><td></td><td>propanol</td><td> 116,5</td><td> 241(15 000)</td><td>H, 7.02</td><td> 7,00</td>

<td> 68</td><td rowspan="2"> <0</td><td>A</td><td> 50,64</td><td>dimethyl</td><td> 164-</td><td> 241(12 200)</td><td>C, 67.58</td><td> 67,60</td>

<td></td><td></td><td></td><td>formamide</td><td> 166</td><td></td><td>H, 7.09</td><td> 7,08</td>

<td></td><td></td><td></td><td></td><td>water</td><td></td><td></td><td>N 19.70</td><td> 19,44</td>

<td></td><td colspan="5">Aryl-2- (1-iraidazolylphenylureylenes)</td><td colspan="2">IV) was prepared by</td><td>turnover</td>

equimolar amounts of the aminophenylimidazole and the appropriate arylisocyanate in dry toluene for 3 hours at steam bath temperature. The reaction mixture was cooled and the crude product was separated by filtration and washed with ether and crystallized from the indicated solvent.

Table IV

460 477

ArNCO

HHCNHAr

Aryl-2- (1-imidazolyl) fenylurey1ener

Are

Yield%

Crystallization Solvent

<td> '0</td><td> 64,6</td><td>ethanol</td>

<td></td><td> 76,9</td><td rowspan="2">dimethylformamide, water</td>

<td>HQ ou</td><td> 76,9</td><td>ethanol</td>

<td>-9 ' F</td><td> 78,8</td><td>dimethylformamide, water</td>

<td>-Q</td><td> 61,9</td><td>dimetylformamidj</td>

<td>F</td><td></td><td>water</td>

<td>O-.</td><td> 65,8</td><td>dimethylformamide, water</td>

<td> 0Cl</td><td> 76,7</td><td>dimethylformamide,</td>

water

Analysis

<td>° C T max (Ajn)</td><td>calculated</td><td>Found</td>

I, 460

477 exchange

Cu3

<td rowspan="2">Kristallίsations- c__ solutionp° C</td><td rowspan="2">Λ max (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td>dimethyl 244-245,</td><td rowspan="2"> 5 260(32 900)</td><td>C, 55.35</td><td> 54,93</td>

<td>formamide,</td><td>H, 3.48</td><td> 3,47</td>

<td>water</td><td></td><td>N, 16.14</td><td> 16,25</td>

<td>dimethyl 180.5-</td><td> 252(23 000)</td><td>C, 53.80</td><td> 53,88</td>

<td>formamide, 182.5</td><td></td><td>H, 3.76</td><td> 3,78</td>

<td>water</td><td></td><td>H, 15.68</td><td> 15,66</td>

<td>dimethyl 218-219,</td><td> 5 258(28.600)</td><td>C, 53.80</td><td> 53,71</td>

<td>formamidet</td><td></td><td>H, 3.67</td><td> 3,66</td>

<td>water</td><td></td><td>N, 15.68</td><td> 15,35</td>

<td>methanol 227-230,</td><td> 5 260(27 700)</td><td>C, 53.80 H, 3.67 N, 15.68</td><td> 52,08 3,56 15,12</td>

<td>dimethyl 201-202</td><td rowspan="2"> 253(26 000)</td><td>C, 64.86</td><td> 64,47</td>

<td>formamide,</td><td>H, 4.42</td><td> 4,40</td>

<td>water</td><td></td><td>N, 18.97</td><td> 19,24</td>

<td>dimethyl 167-170</td><td rowspan="2"> 250(20 710)</td><td>C, 69.84</td><td> 70,10</td>

<td>formamide,</td><td>H, 5.52</td><td> 5,57</td>

<td>water</td><td></td><td>N, 19.17</td><td> 18,60</td>

<td>dimethyl 216.5-</td><td rowspan="2"> 256(31 010)</td><td>C, 58.96</td><td> 58,86</td>

<td>formamide, 218.5</td><td>H, 3.78</td><td> 3,81</td>

<td>water</td><td></td><td>N, 16.18</td><td> 15,79</td>

<td>dimethyl 212-215</td><td rowspan="2"> 260(27 580)</td><td>C, 70.57</td><td> 70,30</td>

<td>formamide,</td><td>H, 5.92</td><td> 5,83</td>

<td>water</td><td></td><td>N, 18.29</td><td> 18,00</td>

<td>dimethyl 185-188</td><td> 258(29 590)</td><td>C, 70.57</td><td> 70,30</td>

<td>formamide,</td><td></td><td>H, 5.92</td><td> 5,96</td>

<td>water</td><td></td><td>N, 18.29</td><td> 18,00</td>

<td>dimethyl 163.5-</td><td> 258(28 770)</td><td>C, 70.57</td><td> 70,52</td>

<td>formamide, 166</td><td></td><td>H, 5.92</td><td> 5,81</td>

<td>water</td><td></td><td>N, 18.29</td><td> 17,94</td>

<td>dimethyl 169-172</td><td rowspan="2"> 257(29 920)</td><td>C, 71.83</td><td> 71,61</td>

<td>formamide,</td><td>H, 6.63</td><td> 6,56</td>

<td>water</td><td></td><td>N, 16.75</td><td> 16,24</td>

<td>dimethyl - 206-209</td><td> 282(27 620)</td><td>C, 71.23</td><td> 71,12</td>

<td>formamide,</td><td></td><td>H, 6.29</td><td> 6,12</td>

<td>water</td><td></td><td> N, 17.49</td><td> 17,24</td>

460 477

Nr. Are93O- ° Yield%

64.1 94 -Ο-,

57,6

<td rowspan="2">Crystallization Solvent</td><td rowspan="2">Mp ° C</td><td rowspan="2">ftmax. (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td>dimethyl</td><td> 202.5-</td><td> 259(35 850)</td><td>C, 71.34</td><td> 71,14</td>

<td>formamide.</td><td> 205</td><td></td><td>Η 4.90</td><td> 4,93</td>

<td>water</td><td></td><td></td><td>Ν 15.13</td><td> 14,78</td>

<td>dimethyl</td><td> 189-191</td><td> 278(32 130)</td><td>C, 62.94</td><td> 62,84</td>

<td>formamide,</td><td></td><td></td><td>Η 4.97</td><td> 4,86</td>

<td>water</td><td></td><td></td><td>Ν 17.27</td><td> 17,22</td>

<td>dimethyl</td><td> 211,5-</td><td> 259(30 210)</td><td>C, 61.45</td><td> 60,94</td>

<td>formamide)</td><td> 214,5</td><td></td><td>Η 4.19</td><td> 4,02</td>

<td>water</td><td></td><td></td><td>Ν 17.91</td><td> 17,79</td>

<td>dimethyl</td><td> 198-210</td><td> 252(25 230)</td><td>C, 61.44</td><td> 61,33</td>

<td>formamide)</td><td></td><td></td><td>Η 3.85</td><td> 3,92</td>

<td>water</td><td></td><td></td><td>Ν 17.83</td><td> 17,98</td>

<td>dimethyl</td><td> 232,5-</td><td> 258(32 380)</td><td>C, 55.35</td><td> 55,60</td>

<td>formamide)</td><td> 234</td><td></td><td>Η 3.48</td><td> 3,50</td>

<td>water</td><td></td><td></td><td>Ν 16.14</td><td> 16,00</td>

<td>dimethyl</td><td> 237,5-</td><td> 258(31 300)</td><td>C, 62.48</td><td> 62,79</td>

<td>formamide)</td><td> 239</td><td></td><td>,6 4.63</td><td> 4,70</td>

<td>water</td><td></td><td></td><td>Ν 17.15</td><td> 17,30</td>

<td>dimethyl</td><td> 229-232</td><td> 256(25 630)</td><td>C, 58.10</td><td> 57,84</td>

<td>formamide)</td><td></td><td></td><td>Η 3.66</td><td> 3,56</td>

<td>water</td><td></td><td></td><td>Ν 16.94</td><td> 16,90</td>

<td>dimethyl</td><td> 239.5-</td><td> 261(37 430)</td><td>C, 53.63</td><td> 53,89</td>

<td>formamide)</td><td> 242,2</td><td></td><td>Η 3.18</td><td> 3,05</td>

<td>water</td><td></td><td></td><td>Ν 14.71</td><td> 14,41</td>

35.2

25.2

<td rowspan="2">Crystallization * solvent</td><td rowspan="2">Mp ° c;</td><td rowspan="2">1 max (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td>dimethyl</td><td> 190-192</td><td> 255(26 350)</td><td>C, 53.63</td><td> 53,70</td>

<td>formamide,</td><td></td><td></td><td>H, 3.18</td><td> 2,97</td>

<td>water</td><td></td><td></td><td>N, 14.71</td><td> 14,90</td>

<td>dimethyl</td><td> 202-205</td><td> 375(4 200)</td><td></td><td></td>

<td>formamide,</td><td></td><td> 253(32 970)</td><td>C, 59.44</td><td> 59,40</td>

<td>water</td><td></td><td></td><td>H, 4.05</td><td> 4,10</td>

<td>dimethyl</td><td> 237,5-</td><td> 342(1 800)</td><td>C, 59.44</td><td> 59,16</td>

<td>formamide,</td><td> 239,5</td><td> 264(46 530)</td><td>H, 4.05</td><td> 4,10</td>

<td>water</td><td></td><td></td><td>N, 21.66</td><td> 21,31</td>

<td>dimethyl</td><td> >257</td><td> 330(20 010)</td><td>C, 59.44</td><td> 59,01</td>

<td>formamidez</td><td>(probe.)</td><td></td><td>H, 4.05</td><td> 3,97</td>

<td>water</td><td></td><td></td><td>N, 21.66</td><td> 21,07</td>

<td>dimethyl</td><td> 256,5-</td><td> 257(33 080)</td><td>C, 53.72</td><td> 53,72</td>

<td>formamide,</td><td> 258</td><td></td><td>H, 3.38</td><td> 3,31</td>

<td>water</td><td></td><td></td><td>N, 19.57</td><td> 19,63</td>

<td>dimethyl</td><td> 254-256</td><td> 256(36 930)</td><td>C, 60.53</td><td> 60,26</td>

<td>formamide,</td><td>(Dec.)</td><td></td><td>H, 4.48</td><td> 4,34</td>

<td>water</td><td></td><td></td><td>N, 20.76</td><td> 20,68</td>

<td>dimethyl</td><td> 244</td><td> 290(57 510)</td><td>C, 67.32</td><td> 67,88</td>

<td>formamide,</td><td></td><td></td><td>H, 4.32</td><td> 4,13</td>

<td>water</td><td></td><td></td><td>N, 23.09</td><td> 21,37</td>

<td>dimethyl</td><td> 233-236</td><td> 284(16 710)</td><td>C, 73.15</td><td> 72,70</td>

<td>formamide,</td><td></td><td></td><td>H, 4.91</td><td> 4,97</td>

<td>water</td><td></td><td></td><td>N, 17.06</td><td> 16,63</td>

<td>dimethyl</td><td> 231-232</td><td> 252(32 920)</td><td>C, 56.31</td><td> 54,13</td>

<td>formamide +</td><td></td><td></td><td>H, 3.55</td><td> 3,50</td>

<td>methanol,</td><td></td><td></td><td>N, 20.52</td><td> 20,21</td>

water

Preparation of 4-Substituted ImidazoZT, 2-α7 quinoxalines

The 4-substituted imidazoZT, 2-§7 quinoxalines are prepared by the general procedures described, starting from counter-acidifying 1- (2-acylaminophenyl) imidazoles. Tables V-VIII below indicate the particular process in question used in the preparation of each compound and also reflect the physical-chemical properties of the compound obtained.

460 477

4-alkylimidazo / T, 2- [7] quinoxalines (Table V) were prepared by refluxing the appropriate amide (Table I, Compounds 2-30) with phosphorus oxychloride in an excess of pyridine for 1 hour. The reaction mixture was stirred in water and a sufficient amount of azeotrope was removed to form a viscous residue, which was dissolved in chloroform, dried over magnesium sulfate and chromatographed through an alumina column. The chloroform was evaporated and the product crystallized from the indicated solvent.

4-alkylimi dazo / T, in noxa1 in down

<td rowspan="2">Nr.</td><td rowspan="2">R</td><td rowspan="2">Exchange %</td><td rowspan="2">Crystallize ten solvents</td><td colspan="2" rowspan="2">mp ° C T max (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td> 110</td><td>CH -</td><td> 13,3</td><td>isopropyl</td><td> 134-135</td><td rowspan="2"> 312(11 200)</td><td>C, 72.11</td><td> 72,18</td>

<td></td><td>u</td><td></td><td>ether</td><td></td><td>H, 4.95</td><td> 4,89</td>

<td> 111</td><td>CH.CH -</td><td> 37,6</td><td>hexane</td><td> 114-115</td><td rowspan="2"> 311(10 500)</td><td>C, 73.07</td><td> 72,85</td>

<td> 112</td><td>CH, CH, CH9-</td><td> 14,3</td><td>hexane</td><td> 110-111</td><td rowspan="2"> 314(10 900)</td><td>C, 73.91</td><td> 73,99</td>

<td> 113</td><td rowspan="2">CH3(CH2)3-</td><td> 17,6</td><td>hexane</td><td> 92-93</td><td> 324(8 000)</td><td>C, 74.64</td><td> 74,34</td>

<td> 117</td><td rowspan="2">CH3(CH2)7-</td><td> 26,3</td><td>isopropyl</td><td> 65- 66</td><td> 311(11 600)</td><td>C, 76.83</td><td> 76,97</td>

<td></td><td></td><td>isopropyl ether</td><td></td><td></td><td>H, 8.24</td><td> 8,20</td>

,460 477

<td rowspan="2">Nr.</td><td rowspan="2">R</td><td rowspan="2">Exchange %</td><td rowspan="2">Crystallization Solvent</td><td rowspan="2">Mp ° C</td><td rowspan="2">71 max (Am)</td><td colspan="3">Analysis</td>

<td colspan="2">calculated</td><td>Found</td>

<td> 118</td><td rowspan="2">CH3(Chrs2)8-</td><td> 9,5</td><td>ethyl ether</td><td> 55- 57</td><td> 307(12 500)</td><td>C</td><td> 77,25</td><td> 77,04</td>

<td></td><td></td><td>hexane</td><td></td><td></td><td></td><td> 8,53</td><td> 8,36</td>

<td> 119</td><td rowspan="2">CH3(CH2)14-</td><td> 24,3</td><td>isopbopyl-</td><td> 73- 75</td><td> 313(11 300)</td><td>C</td><td> 79,11</td><td> 79,03</td>

<td></td><td></td><td>ether</td><td></td><td></td><td>hrs</td><td> 9,82</td><td> 10,02</td>

<td> 120</td><td rowspan="2">CH3(CH2)^6-</td><td> 13,7</td><td>isopropyl</td><td> 79- 81</td><td> 311(11 300)</td><td>C</td><td> 79,11</td><td> 79,54</td>

<td></td><td></td><td>ether</td><td></td><td></td><td>hrs</td><td> 10,14</td><td> 10,12</td>

<td> 121</td><td>(CH)9CHCH9-</td><td> 12,6</td><td>hexanes</td><td> 52- 55</td><td> 314(11 700)</td><td>C</td><td> 74,64</td><td> 74,92</td>

<td> 122</td><td>CF -</td><td> 50,7</td><td>in sopropyl</td><td> 184-187</td><td> 328(10 800)</td><td>C</td><td> 55,70</td><td> 55,94</td>

<td></td><td></td><td></td><td>ether-cloning</td><td></td><td></td><td>hrs</td><td> 2,55</td><td> 2,49</td>

<td></td><td></td><td></td><td>roform</td><td></td><td></td><td>N</td><td> 17,72</td><td> 17,64</td>

<td> 123</td><td rowspan="2">CH2= CH (CH2)8-</td><td> 9,8</td><td>hexanes</td><td> 40- 42</td><td> 309(13 100)</td><td>C</td><td> 78,14</td><td> 77,92</td>

<td> 124</td><td>O-*3’2'</td><td> 16,7</td><td>ethanol</td><td> 140,5- 142</td><td> 312(13 100)</td><td>C hrs</td><td> 78,74 5,05</td><td> 78,59 5,20</td>

<td> 125</td><td>CH, 0CH9-</td><td> 3,1</td><td>toluene</td><td> 96,5-</td><td rowspan="2"> 312(10 600)</td><td>C</td><td> 67,59</td><td> 67,04</td>

<td></td><td>0 c</td><td></td><td>hexane</td><td> 97,5</td><td>hrs</td><td> 5,20</td><td> 5,17</td>

<td> 126</td><td rowspan="2">^^ - ο-αι2-</td><td> 14,5</td><td>ethanol</td><td> 146,5-</td><td> 314(10 400)</td><td>N C</td><td> 19,71 74,17</td><td> 19,93 74,28</td>

<td> 127</td><td></td><td> 37,2</td><td>benzene</td><td> 164-167</td><td> 286(10 500)</td><td>CH</td><td> 79,68 4,83</td><td> 80,38 4,91</td>

<td> 128</td><td> 17,9</td><td>hexane</td><td> 106,5- 107,5</td><td> 310(11 500)</td><td>CH</td><td> 75,31 5,87</td><td> 75,32 ' 5,84</td>

<td> 129</td><td rowspan="2"> 0-</td><td> 2,0</td><td>hexane</td><td> 119-</td><td> 311(11 400)</td><td>C</td><td> 76,46</td><td> 76,65</td>

<td> 130</td><td> 0,8</td><td>in sopropyl</td><td> 133-135</td><td> 312(11 700)</td><td>C</td><td> 77,39</td><td> 77,20</td>

<td></td><td></td><td>ether</td><td></td><td></td><td>hrs</td><td> 5,68</td><td> 6,13</td>

Notes: a. AM Siminov and IG Urykina: Khim. Geterot. Soedin. 7, (1971) 570 reports that this compound has a melting point of 124 ° C with (Am) 31 315 (1°. 7°°).

b. Purified by sublimation at 90 ° / 0.15 mm Hg.

c. Purified by distillation at 174-184 ° / 0.40 mm Hg.

460 477

4-arylimidazo [2-a] quinoxalines (Table VI) were prepared and isolated according to the general procedure described for 4-alkylimidazo / T, 2-a7 quinoxalins with the exceptions set forth in Table VI.

Table VI

NH 4 -Ar + phosphorus oxychloride

4-. aryl imi dazo £ T, 2- <7ki noxa 1 i ner

<td rowspan="2">No.</td><td rowspan="2">Are</td><td rowspan="2">Exchange</td><td rowspan="2">Crystallization Solvent</td><td rowspan="2">mp ° C max (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td> 132</td><td rowspan="2">Q</td><td> 37,2</td><td>tolueniso-</td><td> 149- 334(22.650)</td><td>C, 78.74</td><td> 78,89</td>

<td></td><td></td><td>propanol</td><td> 150,5</td><td>Η 5.05</td><td> 5,08</td>

<td> 133</td><td rowspan="2"></td><td> 35,9</td><td>isopropanol</td><td> -112- 329(15 400)</td><td>C, 78.74</td><td> 78,53</td>

<td></td><td></td><td>isopropyl</td><td> 114</td><td>Η 5.05</td><td> 5,19</td>

<td></td><td>CH</td><td></td><td>ether</td><td></td><td>Ν 16.20</td><td> 16,20</td>

<td> 134</td><td></td><td> 47,1</td><td>isopropanol</td><td> 119-120 329(18 100)</td><td>C, 78.74 Η 5.05</td><td> 78,32 4,73</td>

<td> 135</td><td>oo ·</td><td> 37,8</td><td rowspan="2">isopropanol</td><td> 136-137 331(27 780</td><td>C, 82.22 Η 4.70</td><td> 82,06 4,38</td>

<td> 136</td><td>Q</td><td> 47,0</td><td>isooctane</td><td> 112-113 332(10 411)</td><td>C, 65.18 Η 3.22</td><td> 65,03 3,10</td>

<td> 137</td><td rowspan="2"></td><td> 56,7</td><td>hexanes</td><td> 105-107 329(20 354)</td><td>C, 79.70 Η 6.35</td><td> 79,59 6,58</td>

<td> 138</td><td>"□ θ-Ο-</td><td> 37,2</td><td rowspan="2">isopropanoltoluen</td><td> 149- 334(22 650) 150,5</td><td>C, 74.17 Η 4.76 Ν 15.26</td><td rowspan="2"> 74,18 4,79 15,33</td>

<td> 139</td><td>P</td><td> 51,5</td><td rowspan="2">isopropanol</td><td> 136-138 329(16 600)</td><td>C, 70.81 Η 4.95</td><td> 70,61 5,06</td>

<td>Nr.</td><td>Are</td><td>Exchange %</td><td>Crystal isation solvent</td>

<td> 140</td><td>c~ O ~</td><td> 31,5</td><td>ethanol</td>

<td> 141</td><td>Cl</td><td> 6,8</td><td>bensenhexaner</td>

<td> 142</td><td>p Cl</td><td> 35,2</td><td>isopropanol</td>

<td> 143</td><td>Cl-O-</td><td> 61,9</td><td>toluene</td>

<td> 144</td><td></td><td> 3,4</td><td>carbon tetrachloride</td>

<td> 145</td><td>Q Dr.</td><td> 24,1</td><td>dimethylformamide</td>

<td> 146</td><td> •«-0-</td><td> 13,4</td><td>dimethyl formamide water</td>

<td> 147</td><td>p-O- z</td><td> 39,1</td><td>isopropanol</td>

<td> 148</td><td>- - η V. Q COOH</td><td> 15,0</td><td>ethanol</td>

<td> 149</td><td>•"'O-</td><td> 53,3</td><td>dimetylformamidvatten</td>

<td> 150</td><td>p no2</td><td> 59,8</td><td>2-ethoxyethanol</td>

<td colspan="2">151</td><td> 40,3</td><td>toluene</td>

<td>mp</td><td colspan="2">Analysis</td><td>j</td>

<td rowspan="2">° C / Lmax.(Am)</td><td>Birak -----</td><td>Fun-</td><td>• i</td>

460 477

Crystalline Yield%

sationslösningsmedel

Mp ° C

Max, max. (AM)

Analysis

Do not berak- FurTnat

Nr.

Are

61,9

<td>dimethyl</td><td>283-285 340 (10 880) C 57.30</td>

<td>formamide</td><td>H, 2.71</td>

57,08

2,74

21.11 dimethyl-198formamide-199.5 water

369 (23470) C 73.83

H, 4.65

N, 21.53

73,48

4,69

21,54

154

155 Item No.

58.0 • 1/3 U2 °

173

32,3

<td rowspan="2">dimetylformamidvatten</td><td rowspan="2"> 130-133</td><td colspan="3">326 (14,830) 0 73.83 H, 4.65</td>

<td>ethylacetate-</td><td> 214-217</td><td rowspan="2"> 342(27 700)</td><td>C</td><td> 68,88</td>

<td>hexane</td><td></td><td>hrs</td><td> 4,66</td>

<td>dimethyl</td><td> 237,5-</td><td> 345(32 350)</td><td>-C</td><td> 68,24</td>

<td>formamide</td><td> 240</td><td></td><td>hrs</td><td> 3,90</td>

<td>water</td><td></td><td></td><td>N</td><td> 13,84</td>

<td>ethanol</td><td> 155-157</td><td rowspan="2"> 321(13 090)</td><td>C</td><td> 72,99</td>

73,56

4,78

21,69

68,46

4,99

17,76

68,54

3,90

14,00

72,44

3,83

16,14

157

158

159

160

Dr.

56.6

47,5

52.7

10,62

<td>dimetylformamidvatten</td><td> 134,5- 136</td>

<td>dimetylformanridvatten</td><td> 132,5- 134</td>

<td>ethanol</td><td> 113- 114,5</td>

59,25

3,04

13,11

73,00

3,79

15,84

74,09

4,71

15,05

<td>chloroform 159-</td><td>323 (15290) C 81.34</td>

81,29

4,41

14,22

<td>beasen</td><td> 154,5-</td><td> 340(21 800)</td><td>c</td><td> 81,34</td><td> 81,19</td>

<td>isopropyl</td><td> 210-215</td><td> 343(23 800)</td><td>C</td><td> 68,81</td><td> 68,99</td>

<td>propanol</td><td></td><td></td><td>hrs</td><td> 4,69</td><td> 4,63</td>

460 477

<td></td><td></td><td>crystal-</td><td></td><td></td>

<td></td><td>Out-</td><td rowspan="2">sational c solvent</td><td>Analysis</td><td></td>

<td></td><td>change</td><td>calculations</td><td>Fun-</td>

<td>Nr. Are</td><td> %</td><td>average ° C Λ max. (AM)</td><td>sodium</td><td>net</td>

<td rowspan="2">163 φ- / ® = \ £. CHjCO- ^ y</td><td> 84,2</td><td rowspan="2">ethanol 158-160 333 (14,950)</td><td>C, 71.28</td><td> 71,31</td>

<td>164, fl / = \f80.3 CH3(CH2)2co - ^^ -</td><td>ethanol'</td><td> 116-118</td><td> 335(15 100)</td>

<td> 165/3,,(0,,)^-^-62,6</td><td>ethanol</td><td> 90,5- 93,5</td><td> 335(15 100)</td>

<td>O -u · 1660 * 3 <α · 2> ι4Μ-θ 45.85 • 1/4 112<ϊ</td><td>chloroform</td><td> 154- 155,5</td><td> 344(27 240)</td>

<td> 193 :· 29,80</td><td>ethanol</td><td> 150-152</td><td> 342(22 900)</td>

C, 72.49

H, 5.17

N, 12.68

C, 75.15

H, 7.03

N, 10.11

C, 76.38

H, 8.51

N, 11.14

72,38

5,42

12,36

74,87

7,16

9,94

76,58

8,35

10,81

οη3ο <> ~ O— 9

220 J 35,1

221 .1 / 2 HgO 33.3

<td>dimethylformam rival</td><td> 178-181</td><td> 330(27 300)</td>

<td>toluene</td><td> 151,5- 153,5</td><td> 333(21 100)</td>

<td>benzene</td><td> 151,5- 153,5</td><td> 337(22 200)</td>

<td>ethanol water</td><td> >300°</td><td> 343(22 700)</td>

<td>ethanol</td><td> 83-85</td><td> 348(24,600)</td>

<td>toluene</td><td> 164- 165,5</td><td> 339(19 400)</td>

C, 51.77

H, 2.72

N, 11.32

C, 78.32

H, 4.48

N, 12.45

C, 75.19

H, 4.66

N, 11.44

C, 72.92

H, 4.45

N, 11.60

C, 72.04

H, 5.74

N, 12.60

C, 74.72

H, 5.23

II 14.52

C, 68.05

H, 5.11

N, 12.53

74,37

5,17

14,33

51,89

2,68

11,46

78,32

4,63

12,22

75,42

4,58

11,46

73,21

4,31

11,74

71,64

5,68

12,62

67,70

5,03

12,32 .460 477

Notes to Table VI:

b. Prepared by refluxing equimolar amounts of

2-aminophenylimidazole and phthalic anhydride in toluene under

1/2 hour. Upon cooling, the product separated from the solution.

c. Prepared by catalytic hydrogenation with 10% palladium on carbon of a dimethylformamide solution of the nitro analog; the crude product precipitated with water.

d. Prepared by treating compound 153 in pyridine with the appropriate acid chloride in question, followed by precipitation with water.

e. Prepared by HI cleavage of compound 138.

f. Prepared by treating the lithium salt of compound 162 with the appropriate acid chloride in question in DMF, followed by precipitation with water.

g. Prepared by treating compound 151 with the appropriate nucleophile in question according to the method set forth by Kornblum et al: J. Org. Chem. 41 (1976) 1560.

h. Prepared by HI cleavage of compound 220.

4-alkylaminoimidazo / 1,2-a-quinoxalines (Table VII) were prepared by treating the corresponding alkyl urylenes (Table III) with phosphorus oxychloride and pyridine for 1/2 hour at reflux temperature. The reaction mixture was poured into cold water, and the excess pyridine was removed by azeotropic distillation. The crude product was dissolved in chloroform and passed through an alumina column. After evaporation of the chloroform, the solid was crystallized from the indicated solvent and obtained in the indicated yield.

460 477

Table VII

phosphorus oxychloride

NHR

4-alkylaminoimidazo (1,2-a) quinoxalines

<td rowspan="2">Nr.</td><td rowspan="2">R</td><td rowspan="2">Exchange %</td><td rowspan="2">crystallisation c Λ solvent * ° C</td><td rowspan="2">Max. (AM)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Funnet-</td>

<td> 167</td><td rowspan="2"></td><td> 4,89</td><td>hexane 98.5- 101.5</td><td> 335(11 700)</td><td>C, 72.15 H, 6.81</td><td> 72,02 6,75</td>

<td> 168</td><td rowspan="2">CH3(CH2)2CH2-</td><td> 28,33</td><td colspan="2">isopropyl 102-104 332 (11 480)</td><td>C, 69.97</td><td> 70,12</td>

<td></td><td></td><td>ether</td><td></td><td>H, 6.71</td><td> 6,71</td>

<td> 169</td><td>CH (CH9)9-</td><td> 7,5</td><td>isopropyl- 72-74</td><td> 317(15 800)</td><td>C, 69.00</td><td> 69,14</td>

<td></td><td></td><td></td><td>ether</td><td></td><td>H, 6.24</td><td> 6,35</td>

4-Arylcuninozmidazo / 1,2-a7quinoxalines (Table VIII) were prepared by treating the corresponding arylureylenes (Table IV) with an equimolar amount of phosphorus oxychloride in refluxing pyridine for 1 hour. The cooled reaction mixture was poured into cold water, and the solid raw material which was separated was dissolved in chloroform, dried and allowed to pass through an alumina column. The chloroform was evaporated and the solid raw material crystallized as indicated in Table VIII.

460 477

4-arylaminoimidazo (l, 2-a) quinoxalines

<td></td><td></td><td></td><td>Crystal i-</td><td></td><td></td><td></td><td></td>

<td></td><td></td><td>Out-</td><td>sational</td><td rowspan="2">mp</td><td></td><td>Analysis</td><td></td>

<td></td><td></td><td>change</td><td>solvent</td><td></td><td>calculations</td><td>Fun-</td>

<td>Nr.</td><td>Are</td><td> %</td><td>average</td><td>° C 71</td><td>max. (Am)</td><td>na t</td><td>net</td>

<td> 170</td><td rowspan="2">cr</td><td> 7,2</td><td>ethanol-</td><td> 120-123</td><td rowspan="2"> 304(13 800)</td><td>C, 72.57</td><td> 72,67</td>

<td></td><td></td><td>water</td><td></td><td>H, 4.76 N, 21.16</td><td> 4,71 20,88</td>

<td> 171</td><td> -3-0</td><td> 13,1</td><td>methanol-chloroform</td><td> 151</td><td> 334(20 700)</td><td>C, 74.43 H, 5.14</td><td> 74,16 5,06</td>

<td> 172</td><td>O-</td><td> 11,7</td><td>methanol</td><td> 153-155</td><td rowspan="2"> 330(20 200)</td><td>C, 74.43</td><td> 73,23</td>

<td></td><td> 2</td><td></td><td>chloroform</td><td></td><td>H, 5.14</td><td> 5,26</td>

<td> 174</td><td>oO</td><td> 13,6</td><td>methanol</td><td> 176,5-</td><td> 330(22 200)</td><td>C, 65.26</td><td> 65,04</td>

<td></td><td></td><td></td><td>chloroform</td><td> 178</td><td></td><td>Ή 3.75</td><td> 3,77</td>

<td> 175</td><td>c-O-</td><td> 10,9</td><td>methanol</td><td> 178,5-</td><td rowspan="2"> 344(33 600)</td><td>C, 58.38</td><td> 58,15</td>

<td></td><td></td><td></td><td>chloroform</td><td> 180,5</td><td>H, 3.06</td><td> 3,06</td>

<td> 176</td><td rowspan="2">'-O-</td><td> 18,2</td><td>toluene</td><td> 193,5-</td><td> 332(4 500)</td><td>C, 49.76</td><td> 49,72</td>

<td></td><td></td><td>chloroform</td><td> 195</td><td></td><td>H, 2.87</td><td> 3,10</td>

<td> 177</td><td>O</td><td> 11,5</td><td>ethanol</td><td> 196,5-</td><td rowspan="2"> 324(16 600)</td><td>C, 56.66</td><td> 56,69</td>

<td> 178</td><td>· p</td><td> 15,0</td><td>methanol</td><td> 184-</td><td rowspan="2"> 329(24 100)</td><td>C, 56.66</td><td> 56,26</td>

<td></td><td rowspan="2">hr</td><td></td><td>chloroform</td><td> 185,5</td><td>H, 3.27</td><td> 3,20</td>

460 477

crystal-

<td>Nr.</td><td>Are</td><td>Exchange %</td><td>sationslösningsmedel</td>

<td> 179</td><td></td><td> 10,52</td><td rowspan="2">dimethylformamics</td>

<td> 180</td><td>'Q-</td><td> 13,0</td><td>etanoldimetyl-</td>

<td></td><td>F</td><td></td><td>formamide</td>

<td> 181</td><td>Q-</td><td> 9,4</td><td>isopropyl</td>

<td></td><td>F</td><td></td><td>propanol</td>

<td> 182</td><td>-O-</td><td> 3,1</td><td>isopropanol</td>

<td rowspan="2">Mp ° C</td><td rowspan="2">On max. (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

<td> 16,58</td><td>dimethyl -</td><td> 166-</td><td> 347(21 730</td><td colspan="2">C, 56.66</td><td> 56,31</td>

<td></td><td>formamide</td><td> 168,5</td><td></td><td>hrs</td><td> 3,27</td><td> 3,25</td>

<td></td><td>water</td><td></td><td></td><td>N</td><td> 16,52</td><td> .16,56</td>

<td rowspan="2">isopropanol-dimethylformamide</td><td rowspan="2"> 195-197</td><td rowspan="2">341 (20 + 37 /)) in</td><td colspan="2">C, 60.28</td><td rowspan="2"> 60,21 3,88 21,63</td>

<td>dimethyl</td><td> 241-</td><td rowspan="2"> 400(8 960)</td><td>C</td><td> 62,95</td><td> 62,62</td>

<td>fonnamid-</td><td> 243,5</td><td>hrs</td><td> 3,63</td><td> 3,63</td>

<td>water</td><td></td><td></td><td>N</td><td> 22,94</td><td> 22,68</td>

<td>dimethyl</td><td> 323-</td><td> 368(23 670)</td><td>C</td><td> 62,95</td><td> 62,73</td>

<td>formamiri-</td><td> 324,5</td><td></td><td>hrs</td><td> 3,63</td><td> 3,73</td>

<td>water</td><td></td><td></td><td>N</td><td> 22,94</td><td> 22,81</td>

.460 477

<td></td><td></td><td></td><td>Crystal i-</td>

<td></td><td></td><td>Out-</td><td>sational</td>

<td></td><td></td><td>change</td><td>solvent</td>

<td>Nr.</td><td>Are</td><td> %</td><td>average</td>

<td> 195</td><td> 0-0</td><td> 11,61</td><td>dimethylformamide</td>

<td></td><td></td><td></td><td>water</td>

<td> 197</td><td>Q?</td><td> 5,52</td><td>dimethylformamide</td>

<td></td><td>Cilj</td><td></td><td>water</td>

<td> 198</td><td>«□ -θ '</td><td> 10,91</td><td>dimethyl</td>

<td></td><td>/ cII3</td><td></td><td>water</td>

<td> 199</td><td> /</td><td> 15,29</td><td>dimethyl</td>

<td></td><td>CHjQIj</td><td></td><td>formamidvatten</td>

<td> 200</td><td colspan="2">r »~ / = \ ,3·81-VI n20</td><td>dimetylformamidvatten</td>

<td> 201</td><td></td><td> 16,96</td><td>isopropanol</td>

<td></td><td> /=\</td><td></td><td>water</td>

<td rowspan="2"> • 202</td><td rowspan="2">-W h2O</td><td rowspan="2">methanol-chloroform</td>

<td> 205</td><td rowspan="2">cV </> - iz ·!/<</td><td> 8,5 11,0</td><td>dimethylformamide</td>

<td></td><td></td><td>water</td>

<td> 206</td><td>Q</td><td> 21,39</td><td>dimethylformamide</td>

<td></td><td>XFj</td><td></td><td>water</td>

<td rowspan="2">Mp ° C</td><td rowspan="2">K max (Am)</td><td colspan="2">Analysis</td>

<td>calculated</td><td>Found</td>

460 477

Kristallί-

<td></td><td>Out-</td><td rowspan="2">sation <solution p</td><td></td><td>Analysis</td><td></td>

<td></td><td>change</td><td></td><td>calculations</td><td>Fun-</td>

<td>Nr. Are</td><td> %</td><td colspan="2">medium C 4 max (Am)</td><td>na t</td><td>net</td>

<td rowspan="2">207 «-Q CF ·</td><td> 11,49</td><td>dimethyl-78,5-</td><td> 324(25 500)</td><td>C, 56.29</td><td>55.86 I</td>

<td></td><td>formamide 179.5</td><td></td><td>H, 2.78</td><td> 2,72</td>

<td>M3</td><td></td><td>water</td><td></td><td>N, 15.45</td><td> 15,37</td>

<td rowspan="2"> 208</td><td> 7,52</td><td>dimethyl 172.5-</td><td rowspan="2"> 345(24 900)</td><td>C, 56.29</td><td> 56,13</td>

<td></td><td>formamide 173.5</td><td>H, 2.78</td><td> 2,72</td>

<td>cr3</td><td></td><td>water ·</td><td></td><td>H, 15.45</td><td> 15,35</td>

<td>209 C ,,3 "O</td><td> 15,18</td><td>dimethyl 170-172 formamide</td><td> 332(23 800)</td><td>C, 65.18 H, 4.18</td><td> 65,35 4,15</td>

<td>/ Ί / 4 Cl</td><td> »20</td><td>water</td><td></td><td>N, 17.89</td><td> 17,91</td>

<td>210 'Q</td><td> 13,56</td><td>dimethyl 171.5formamide 173</td><td> 337(17 300)</td><td>C, 64.86 H, 3.40</td><td> 64,92 3,51</td>

<td>F</td><td></td><td>water</td><td></td><td>N, 18.91</td><td> 19,09</td>

<td> 211 7*\</td><td> 10,78</td><td>dimethyl 259.5-</td><td rowspan="2"> 342(23 200)</td><td>C, 56.82</td><td> 56,76</td>

<td>SJ -1/2</td><td>If2O</td><td>formamide 261.5</td><td>H, 3.28</td><td> 3,07</td>

<td>2i</td><td></td><td>water</td><td></td><td>N, 16.57</td><td> 16,57</td>

<td rowspan="2"> 212 F-O Cl</td><td> 7,22</td><td>dimethyl 198-200 formamide</td><td> 343(18 400)</td><td>C, 61.45 H, 3.22</td><td> 61,35 3,27</td>

<td></td><td>water</td><td></td><td>N, 17.92</td><td> 17,81</td>

<td> 213F~ O ~ / -7 * 1/4 ll20</td><td> 3,04</td><td>methanol-229-231 chloroform</td><td> 341(19 900)</td><td>C, 58.63 H, 3.15</td><td> 58,50 3,06</td>

<td> 214α · 3 Ο *</td><td> 4,18</td><td>methanol 168-170</td><td rowspan="2"> 344(21 400)</td><td>C, 63.06</td><td> 62,97</td>

<td>NO2 -1/4 II2</td><td> 0</td><td>chloroform</td><td>H, 4.12 N, 21.63</td><td> 4,08 21,34</td>

<td>215 Cl-p-</td><td> 19,43</td><td>dimethyl 271-273 formamide</td><td> 346(19 600)</td><td>C, 56.57 H, 2.97</td><td>56.44 I 2.90 1</td>

<td>NQ2</td><td></td><td>water</td><td></td><td>N, 20.61</td><td> 20,51 [</td>

<td rowspan="2"> 216</td><td> 5,96</td><td>dimethyl-224-</td><td> 349(34 700)</td><td>C, 70.48</td><td> 70,89 1</td>

<td></td><td>formamide-226.5</td><td></td><td>H, 3.91</td><td>3.94 t</td>

<td></td><td></td><td>water</td><td></td><td>N, 24.17</td><td>24.09 I</td>

<td rowspan="2"> 218((^3)201-O"</td><td> 2,31</td><td>isopro- 95-96.5</td><td></td><td>C, 75.47</td><td> 75,08 1</td>

<td></td><td rowspan="2">propanol</td><td></td><td>H, 6.00</td><td>b, 34 S.</td>

<td colspan="2">Note: a. All data</td><td>refers to the l / 4-hy << rate</td><td></td><td></td><td></td>

460 477

Various compounds of formula I exhibit antifungal activity and anti-yeast activity. The compounds have e.g. has been shown to be effective against such organisms as Candida albicans (ATCC No. 10231), Candida tropicalis, Aspergillus niger (ATCC No. 16404), Trichophyton mentagrophytes (ATCC No. 8757 and 9129), Trichophyton rubrum (ATCC No. 10218 and 14001) also Trichophyton ajelloi.

The antifungal activity of the compounds of formula I suggests their utility in the treatment of dermatomycoses such as tinea capitis, tinea favosa, tinea barbae, tinea corporis, tinea imbricata, tinea cruris, tinea pedis, tinea manus, and tinea unquium and various types of candidiasis such as glossite , stomatite, chelite, perish, vaginite and balanite.

A number of the compounds of formulas I and II have been found to have immunosuppressive activity. Of the compounds tested, most are of the 4-substituted imidazo / T, 2-α-quinoxaline type of formula I above, although some belong to the 1- (2-acylaminophenyl) imidazole type of formula II. Because they exhibit this effect, they can be used to treat those diseases which in the art are considered to be treatable by administration of immunosuppressive agents. These diseases include conditions such as glomerulonephritis, serum diseases, organ transplants, rheumatoid arthritis, systemic lupus etythematosus, ulcerative colitis, chronic active hepatitis, multiple sclerosis, heteroplasty or homoplasty in burns, psoriatic arthritis, hay fever, urticaria, respiratory sclera, mycosis fungoides, dertatomyositis, psoriasis and contact dermatitis (including poison sumac).

A number of compounds of formulas I and II exhibit non-steroidal anti-inflammatory activity. This appears to be generally true of the 4-substituted imidazo / 1,2-a-quinoxalines of formula I above and the 1- (2-acylaminophenyl) imidazoles of formula II above. Because of this property, the compounds can be used in the treatment of diseases which in the art are considered to be remedied by the administration of non-steroidal anti-inflammatory compounds. These diseases include conditions such as ichthyosis, psoriasis, alopecia, atopic eczema, etc.

460 477

54 members in 19 offices

This recordMember, by publication datePriority claim9 more offices are in the list below

Priority claims4

Priority claims
Document	Office	Kind	Date
75764077	United States of America	A	1977-01-07
75764077	United States of America	A	1977-01-07
757640	–	–	–
US19770757640	–	–	–

Members54

Family members, oldest first
Document	Office	Kind
BE862608A	Belgium	A	1978-07-03
IE780037L	Ireland	L	1978-07-07
IE810213L	Ireland	L	1978-07-07
DK4278A	Denmark	A	1978-07-08
FI780023A	Finland	A	1978-07-08
FI780023A7	Finland	A7	1978-07-08
SE7800138L	Sweden	L	1978-07-08
NL7800114A	Netherlands (Kingdom of the)	A	1978-07-11
DE2800480A1	Germany	A1	1978-07-13
JPS5387398A	Japan	A	1978-08-01
FR2376858A1	France	A1	1978-08-04
LU78813A1	Luxembourg	A1	1978-09-18
ZA7827B	South Africa	B	1979-01-31
US4160097A	United States of America	A	1979-07-03
AU3233178A	Australia	A	1979-07-19
US4172947A	United States of America	A	1979-10-30
US4191766A	United States of America	A	1980-03-04
US4191767A	United States of America	A	1980-03-04
US4197403A	United States of America	A	1980-04-08
US4198508A	United States of America	A	1980-04-15
US4200750A	United States of America	A	1980-04-29
CS200232B2	Czechoslovakia (until 1993)	B2	1980-08-29
US4225724A	United States of America	A	1980-09-30
US4229452A	United States of America	A	1980-10-21
FR2376858B1	France	B1	1980-10-24
GB1579498A	United Kingdom	A	1980-11-19
GB1579499A	United Kingdom	A	1980-11-19
US4236015A	United States of America	A	1980-11-25
FI821308L	Finland	L	1982-04-14
AU521807B2	Australia	B2	1982-04-29
SE8300945D0	Sweden	D0	1983-02-21
SE8300945L	Sweden	L	1983-02-21
IE46191B1	Ireland	B1	1983-03-23
IE46192B1	Ireland	B1	1983-03-23
CH636102A5	Switzerland	A5	1983-05-13
CA1149385A	Canada	A	1983-07-05
FI64374B	Finland	B	1983-07-29
FI64375B	Finland	B	1983-07-29
FI64374C	Finland	C	1983-11-10
FI64375C	Finland	C	1983-11-10
CH640229A5	Switzerland	A5	1983-12-30
GR73168B	Greece	B	1984-02-14
CA1164877A	Canada	A	1984-04-03
SE436359B	Sweden	B	1984-12-03
JPS61171470A	Japan	A	1986-08-02
JPS6259110B2	Japan	B2	1987-12-09
JPH0130825B2	Japan	B2	1989-06-22
SE460477BThis record	Sweden	B	1989-10-16
DK157024B	Denmark	B	1989-10-30
DK157024C	Denmark	C	1990-04-02
DE2858766C2	Germany	C2	1990-04-05
DE2800480C2	Germany	C2	1990-04-12
YU2178A	Yugoslavia, later Serbia and Montenegro (until 2006)	A	1990-04-30
YU44663B	Yugoslavia, later Serbia and Montenegro (until 2006)	B	1990-12-31

Abstract

Term

II

III

W '

C, 61.6360.97

H, 3,653.62

N, 12.6812.34

FF

FF

IN

C

I, 460

369 (23470) C 73.83

H, 4.65

N, 21.53

C, 72.49

H, 5.17

N, 12.68

C, 75.15

H, 7.03

N, 10.11

C, 76.38

H, 8.51

N, 11.14

C, 51.77

H, 2.72

N, 11.32

C, 78.32

H, 4.48

N, 12.45

C, 75.19

H, 4.66

N, 11.44

C, 72.92

H, 4.45

N, 11.60

C, 72.04

H, 5.74

N, 12.60

C, 74.72

H, 5.23

II 14.52

C, 68.05

H, 5.11

N, 12.53

NHR

Priority claims4

Members54

Events

Numbers

Titles2

Classification